The development of drug-eluting stents (DES) is one of the critical milestones in the advances of interventional cardiology. However, clinical stent thrombosis still poses a serious potential complication. In acute ST-segment elevation myocardial infarction (STEMI), acute total vessel occlusion has a larger thrombus burden, and the use of DES in this particular setting raises safety concerns. Published data from randomized, controlled studies, observational studies and recently published meta-analyses mostly support the safety of DES use in acute STEMI. However, these studies have limited study populations and follow-up periods, so the long-term safety of DES in the setting of STEMI is still unclear, and careful consideration should be given in clinical decision-making. In this article we reviewed the findings of randomized and nonrandomized trials on the use of drugeluting versus bare-metal stents in the setting of acute STEMI.